tbuckley/cabot-search huggingface dataset:
Textbook outcomes in liver surgery for gallbladder cancer patients treated with curative-intent resection: a multicenter observational study
Authors: Zhi-Peng Liu, Wei Guo, Da-Long Yin, Wei-Yue Chen, Jiao-Yang Wang, Xue-Lei Li, Ping Yue, Chao Yu, Zhao-Ping Wu, Rui Ding, Yi Zhu, Fan Huang, Jin-Xue Zhou, Dong Zhang, Wei Chen, Yan Jiang, Jie Bai, Jing-Jing Wang, Yan-Qi Zhang, Hai-Su Dai, Wan Yee Lau, Zhi-Yu Chen
Journal: International Journal of Surgery (2023)

Cholecystectomy, hepatectomy, and lymphadenectomy are recommended as the curative treatment for resectable gallbladder cancer (GBC). Textbook outcomes in liver surgery (TOLS) is a novel composite measure that has been defined by expert consensus to represent the optimal postoperative course after hepatectomy. This study aimed to determine the incidence of TOLS and the independent predictors associated with TOLS after curative-intent resection in GBC patients.All consecutive GBC patients who underwent curative-intent resection between 2014 and 2020 were enrolled from a multicenter database from 11 hospitals as the training and the internal testing cohorts, and Southwest Hospital as the external testing cohort. TOLS was defined as no intraoperative grade greater than or equal to 2 incidents, no grade B/C postoperative bile leaks, no postoperative grade B/C liver failure, no 90-day postoperative major morbidity, no 90-day readmission, no 90-day mortality after hospital discharge, and R0 resection. Independent predictors of TOLS were identified using logistic regression and were used to construct the nomogram. The predictive performance was assessed using the area under the curve and calibration curves.TOLS was achieved in 168 patients (54.4%) and 74 patients (57.8%) from the training and internal testing cohorts, and the external testing cohort, respectively. On multivariate analyses, age less than or equal to 70 years, absence of preoperative jaundice (total bilirubin≤3 mg/dl), T1 stage, N0 stage, wedge hepatectomy, and no neoadjuvant therapy were independently associated with TOLS. The nomogram that incorporated these predictors demonstrated excellent calibration and good performance in both the training and external testing cohorts (area under the curve: 0.741 and 0.726).TOLS was only achieved in approximately half of GBC patients treated with curative-intent resection, and the constructed nomogram predicted TOLS accurately.
Developing evidence-informed indicators to monitor HIV pre-exposure prophylaxis programmes across EU/EEA countries: a multi-stakeholder consensus
Authors: Jef Vanhamel, Eline Wijstma, Jessika Deblonde, Marie Laga, Bea Vuylsteke, Christiana Nöstlinger, Teymur Noori
Journal: Eurosurveillance (2023)

Several countries in the European Union (EU) and European Economic Area (EEA) established and/or scaled up HIV pre-exposure prophylaxis (PrEP) programmes between 2016 and 2023. Data on PrEP programmes’ performance and effectiveness in reaching those most in need will be needed to assess regional progress in the roll-out of PrEP. However, there is a lack of commonly defined indicators for routine monitoring to allow for minimum comparability. We propose a harmonised PrEP monitoring approach for the EU/EEA, based on a systematic and evidence-informed consensus-building process involving a broad and multidisciplinary expert panel. We present a set of indicators, structured along relevant steps of an adapted PrEP care continuum, and offer a prioritisation based on the degree of consensus among the expert panel. We distinguish between ‘core’ indicators deemed essential for any PrEP programme in the EU/EEA, vs ‘supplementary’ and ‘optional’ indicators that provide meaningful data, yet where experts evaluated their feasibility for data collection and reporting as very context-dependent. By combining a standardised approach with strategic opportunities for adaptation and complementary research, this monitoring framework will contribute to assess the impact of PrEP on the HIV epidemic in Europe.
Genetic characterization of ABT-199 sensitivity in human AML
Authors: Richard Bisaillon, Céline Moison, Clarisse Thiollier, Jana Krosl, Marie-Eve Bordeleau, Bernhard Lehnertz, Vincent-Philippe Lavallée, Tara MacRae, Nadine Mayotte, Caroline Labelle, Geneviève Boucher, Jean-François Spinella, Isabel Boivin, Giovanni D’Angelo, Sylvie Lavallée, Anne Marinier, Sébastien Lemieux, Josée Hébert, Guy Sauvageau
Journal: Leukemia (2019)
Covid-19: Metformin reduces the risk of developing long term symptoms by 40%, study finds
Authors: Jacqui Wise
Journal: BMJ (2023)

Covid-19: Metformin reduces the risk of developing long term symptoms by 40%, study finds Jacqui WiseMetformin-a cheap, safe, and widely available diabetes drug-could reduce the incidence of long covid if given during the acute phase of covid-19, a new study indicates. 1 A two week course of metformin given within three days of testing positive for SARS-CoV-2 led to 40% fewer long covid diagnoses over the following 10 months compared with people who had taken placebo, according to a randomised controlled trial.The authors of the study, published in Lancet Infectious Diseases, caution that the trial did not look at whether metformin would be effective as a treatment for those who already have long covid.
Physical Activity Over the Lifecourse and Cardiovascular Disease
Authors: Andrew S. Perry, Erin E. Dooley, Hiral Master, Nicole L. Spartano, Evan L. Brittain, Kelley Pettee Gabriel
Journal: Circulation Research (2023)

Despite improvements in cardiovascular care in recent decades, cardiovascular disease (CVD) remains a leading cause of death worldwide. At its core, CVD is a largely preventable disease with diligent risk factor management and early detection. As highlighted in the American Heart Association's
Pregnancy as an Early Cardiovascular Moment: Peripartum Cardiovascular Health
Authors: Sadiya S. Khan, Natalie A. Cameron, Kathryn J. Lindley
Journal: Circulation Research (2023)

Pregnancy is commonly referred to as a window into future CVH (cardiovascular health). During pregnancy, physiological adaptations occur to promote the optimal growth and development of the fetus. However, in approximately 20% of pregnant individuals, these perturbations result in cardiovascular and metabolic complications, which include hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and small-for-gestational age infant. The biological processes that lead to adverse pregnancy outcomes begin before pregnancy with higher risk of adverse pregnancy outcomes observed among those with poor prepregnancy CVH. Individuals who experience adverse pregnancy outcomes are also at higher risk of subsequent development of cardiovascular disease, which is largely explained by the interim development of traditional risk factors, such as hypertension and diabetes. Therefore, the peripartum period, which includes the period before (prepregnancy), during, and after pregnancy (postpartum), represents an early cardiovascular moment or window of opportunity when CVH should be measured, monitored, and modified (if needed). However, it remains unclear whether adverse pregnancy outcomes reflect latent risk for cardiovascular disease that is unmasked in pregnancy or if adverse pregnancy outcomes are themselves an independent and causal risk factor for future cardiovascular disease. Understanding the pathophysiologic mechanisms and pathways linking prepregnancy CVH, adverse pregnancy outcomes, and cardiovascular disease are necessary to develop strategies tailored for each stage in the peripartum period. Emerging evidence suggests the utility of subclinical cardiovascular disease screening with biomarkers (eg, natriuretic peptides) or imaging (eg, computed tomography for coronary artery calcium or echocardiography for adverse cardiac remodeling) to identify risk-enriched postpartum populations and target for more intensive strategies with health behavior interventions or pharmacological treatments. However, evidence-based guidelines focused on adults with a history of adverse pregnancy outcomes are needed to prioritize the prevention of cardiovascular disease during the reproductive years and beyond.
Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine
Authors: Andrea A. Baccarelli, José Ordovás
Journal: Circulation Research (2023)

Epigenetics has transformed our understanding of the molecular basis of complex diseases, including cardiovascular and metabolic disorders. This review offers a comprehensive overview of the current state of knowledge on epigenetic processes implicated in cardiovascular and metabolic diseases, highlighting the potential of DNA methylation as a precision medicine biomarker and examining the impact of social determinants of health, gut bacterial epigenomics, noncoding RNA, and epitranscriptomics on disease development and progression. We discuss challenges and barriers to advancing cardiometabolic epigenetics research, along with the opportunities for novel preventive strategies, targeted therapies, and personalized medicine approaches that may arise from a better understanding of epigenetic processes. Emerging technologies, such as single-cell sequencing and epigenetic editing, hold the potential to further enhance our ability to dissect the complex interplay between genetic, environmental, and lifestyle factors. To translate research findings into clinical practice, interdisciplinary collaborations, technical and ethical considerations, and accessibility of resources and knowledge are crucial. Ultimately, the field of epigenetics has the potential to revolutionize the way we approach cardiovascular and metabolic diseases, paving the way for precision medicine and personalized health care, and improving the lives of millions of individuals worldwide affected by these conditions.
Diet and Food and Nutrition Insecurity and Cardiometabolic Disease
Authors: Eric J. Brandt, Dariush Mozaffarian, Cindy W. Leung, Seth A. Berkowitz, Venkatesh L. Murthy
Journal: Circulation Research (2023)

Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic disease. Food insecurity is an example of a powerful social determinant of health that impacts health outcomes. Nutrition insecurity, a distinct but related concept to food insecurity, is a direct determinant of health. In this article, we provide an overview of how diet in early life relates to cardiometabolic disease and then continue to focus on the concepts of food insecurity and nutrition insecurity. In the discussions herein we make important distinctions between the concepts of food insecurity and nutrition insecurity and provide a review of their concepts, histories, measurement and assessment devices, trends and prevalence, and links to health and health disparities. The discussions here set the stage for future research and practice to directly address the negative consequences of food and nutrition insecurity.
Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease
Authors: Curtis L. Gabriel, Jane F. Ferguson
Journal: Circulation Research (2023)

Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.
Predictors of sentinel lymph node metastasis in very thin invasive melanomas
Authors: Hanna Kakish, James Sun, David X Zheng, Fasih Ali Ahmed, Mohamedraed Elshami, Alexander W Loftus, Lee M Ocuin, John B Ammori, Richard S Hoehn, Jeremy S Bordeaux, Luke D Rothermel
Journal: British Journal of Dermatology (2023)

Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients.To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas.The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses.Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively.Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB.
Vertical Appearance of Urinary Bladder on Bone Scintigraphy Might Not Always Suggest Adjacent Pathology
Authors: Min Hao, Zhiping Deng, Fuqiang Shao
Journal: Clinical Nuclear Medicine (2023)

Abstract Previous publications suggested that vertical appearance of the urinary bladder on 99m Tc-MDP whole-body bone scintigraphy was likely due to an adjacent abnormality. Here we report bone scan findings of a vertical appearance of the urinary bladder in a 66-year-old man with lung cancer without corresponding pathology nearby.
Herpes Simplex Encephalitis
Authors: Richard J. Whitley, Seng-Jaw Soong, Martin S. Hirsch, Adolf W. Karchmer, Raphael Dolin, George Galasso, June K. Dunnick, Charles A. Alford
Journal: New England Journal of Medicine (1981)

To learn more about the treatment of herpes simplex encephalitis with vidarabine, we conducted an uncontrolled study of 132 patients referred to 22 hospitals because of suspected disease. All had a brain biopsy and were started on vidarabine, but only 75 were diagnosed by isolation of virus from a brain-biopsy specimen. Cumulative mortality in the latter group was 39 per cent at one year. Other than therapy, levels of consciousness and age were the major variables that influenced outcome. Of 23 patients under 30 years of age who were lethargic at the initiation of therapy, two died and 16 returned to normal. Of 26 patients over 30 years of age who were lethargic at the outset, nine died and 10 returned to normal. Semicoma and coma were associated with worse outcomes, especially in older patients. Our data suggest that outcome is improved with treatment; they provide more support for the use of brain biopsy to diagnose the infection and indicate a need for better therapy. (N Engl J Med. 1981; 304:313–8.)
Functional annotation map of natural compounds in traditional Chinese medicines library: TCMs with myocardial protection as a case
Authors: Xudong Xing, Mengru Sun, Zifan Guo, Yongjuan Zhao, Yuru Cai, Ping Zhou, Huiying Wang, Wen Gao, Ping Li, Hua Yang
Journal: Acta Pharmaceutica Sinica B (2023)

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.
Radioembolization Planning With Dual-Isotope Acquisition of 166Ho-Labeled Microparticles and 99mTc-Mebrofenin
Authors: Sándor Czibor, András Bibok, Dénes Horváthy, Krisztián Fábián, Tamás Györke
Journal: Clinical Nuclear Medicine (2023)

Abstract A 76-year-old man with hepatocellular carcinoma was referred for liver radioembolization. Given a prior left hemihepatectomy, it was clinically important to consider potentially irradiated healthy liver at planning. Thus, at the SPECT/CT imaging of the scout dose 166 Ho-microparticles before injected superselectively in the right hepatic artery, 99m Tc-mebrofenin was injected intravenously, and functional volumetry SPECT was performed simultaneously. Based on the 2 image sets, the nonirradiated healthy liver was calculated as 1589 mL (functional liver reserve of 85.5% on 99m Tc-mebrofenin SPECT). Posttreatment dosimetry calculations showed optimal normal tissue and tumor absorbed doses, and the patient is clinically well after 3 months.
Peritoneal Carcinomatosis From Metastatic Prostate Cancer Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT
Authors: Kin Sing Lau, Ken Le, Chuong Bui, Veronica Chi Ken Wong, Robert Mansberg
Journal: Clinical Nuclear Medicine (2023)

Abstract A 69-year-old man with locally advanced prostate adenocarcinoma (Gleason score 9), who had completed hormone therapy and definitive radiotherapy, presented to hospital with abdominal pain and distension. A CT scan of the abdomen and pelvis revealed ascites and extensive peritoneal/omental nodules. Serum prostate-specific antigen was not raised (0.07 μg/L). 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT demonstrated PSMA-avid disease in the prostate and widespread PSMA-avid peritoneal/omental and liver metastases but with no PSMA-avid bony metastases. Peritoneal nodule biopsy confirmed metastatic prostate cancer.
Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials
Authors: Xianjing Chu, Wentao Tian, Ziqi Wang, Jing Zhang, Rongrong Zhou
Journal: Molecular Cancer (2023)

Abstract Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for a substantial number of cancer patients. However, the response rates to ICIs vary significantly among individuals and cancer types, with a notable proportion of patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed as a potential strategy to address these challenges. One of the targets is TIGIT, an inhibitory receptor associated with T-cell exhaustion. TIGIT has diverse immunosuppressive effects on the cancer immunity cycle, including the inhibition of natural killer cell effector function, suppression of dendritic cell maturation, promotion of macrophage polarization to the M2 phenotype, and differentiation of T cells to regulatory T cells. Furthermore, TIGIT is linked with PD-1 expression, and it can synergize with PD-1/PD-L1 blockade to enhance tumor rejection. Preclinical studies have demonstrated the potential benefits of co-inhibition of TIGIT and PD-1/PD-L1 in enhancing anti-tumor immunity and improving treatment outcomes in several cancer types. Several clinical trials are underway to evaluate the safety and efficacy of TIGIT and PD-1/PD-L1 co-inhibition in various cancer types, and the results are awaited. This review provides an overview of the mechanisms of TIGIT and PD-1/PD-L1 co-inhibition in anti-tumor treatment, summarizes the latest clinical trials investigating this combination therapy, and discusses its prospects. Overall, co-inhibition of TIGIT and PD-1/PD-L1 represents a promising therapeutic approach for cancer treatment that has the potential to improve the outcomes of cancer patients treated with ICIs.
Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial
Authors: Emmanuel S. Antonarakis, Se Hoon Park, Jeffrey C. Goh, Sang Joon Shin, Jae Lyun Lee, Niven Mehra, Ray McDermott, Núria Sala-Gonzalez, Peter C. Fong, Richard Greil, Margitta Retz, Juan Pablo Sade, Patricio Yanez, Yi-Hsiu Huang, Stephen D. Begbie, Rustem Airatovich Gafanov, Maria De Santis, Eli Rosenbaum, Michael P. Kolinsky, Felipe Rey, Kun-Yuan Chiu, Guilhem Roubaud, Gero Kramer, Makoto Sumitomo, Francesco Massari, Hiroyoshi Suzuki, Ping Qiu, Jinchun Zhang, Jeri Kim, Christian H. Poehlein, Evan Y. Yu
Journal: Journal of Clinical Oncology (2023)

There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.